Controlling Esophageal Cancer: A Collaborative Modeling Approach. The ultimate goal of the proposed research project is to advance our understanding of esophageal cancer and the impact of cancer control interventions to diminish the burden of this disease. This will be accomplished through a collaborative and comparative modeling project. There are two main histologic types of esophageal cancer: adenocarcinoma (EAC) and Squamous Cell Carcinoma (ESCC). Although ESCC is more common globally, in the US and much of the western world, EAC is more common and of greater concern. Esophageal AdenoCarcinoma (EAC) has experienced a remarkable (more than 6-fold) increase in incidence over the past few decades, which is largely unexplained. To date, primary screening and prevention efforts have targeted patients with symptoms of gastroesophageal reflux disease (GERD) using endoscopy and biopsy to identify patients with Barrett's esophagus (BE), with BE patients targeted for endoscopic surveillance. There is no firm evidence indicating that this screening/surveillance strategy is effective, which is underscored by persistently poor survival rates while a large proportion of cancers continue to be diagnosed at late and invasive stages. With an estimated 40-60 million Americans with GERD and 3-12 million with BE, the management of patients who are at significantly increased risk of EAC has become an important public health issue. In addition to uncertain long-term benefits, current unproven strategies may subject patients to overtesting and overdiagnosis, negatively impacting patient quality of life while expending considerable medical resources. The research team's prior work includes comparative modeling of the natural history of EAC by three independent models providing a strong foundation upon which to perform analyses that assess and improve screening and prevention strategies: specifically, the evaluation of cutting-edge enhancements such as new screening technologies, prevention, genomic and other biomarkers, and clinical prediction tools. Precision risk stratification is the aim, with the broader goal to identify a caner control strategy that is effective while limiting overtesting and overtreatment, thereby reducing patient burden and improving healthcare efficiency. These modeling efforts will provide the personalized patient data necessary to construct a decision aid, which will minimize patient screening burden by aligning management choices with personal preferences for screening. Finally, although the initial focus of the project will be on EAC, ESCC is more common and widespread globally, particularly in parts of Asia such as China. The models will be extended to include an ESCC natural history component and assess ESCC screening in the US and China. The proposal will address the overarching goals of increasing our understanding of the natural history of esophageal cancer and determining the impact and of potential cancer control interventions with the ultimate goal of ameliorating cancer morbidity.